Prospects for Cell-Directed Curative Therapy of Phenylketonuria (PKU)

Molecular Frontiers Journal
Cary O Harding

Abstract

Phenylketonuria (PKU) due to recessively inherited phenylalanine hydroxylase (PAH) deficiency is among the most common inborn errors of metabolism. Dietary therapy begun early in infancy prevents the major manifestations of the disease but shortcomings to treatment continue to exist including lifelong commitment to a complicated and unpalatable diet, poor adherence to diet in adolescence and adulthood, and consequently a range of unsatisfactory outcomes, including neuropsychiatric disorders, frequently develop. Novel treatments that do not strictly depend upon dietary protein restriction are actively sought. This review discusses the potential for and the limitations of permanently curative cell-directed treatment of PKU, including liver-directed gene therapy and gene editing, if initiated during early infancy. A fictional but realistic vignette of a family with a new baby girl recently diagnosed with PKU is presented. What is needed to permanently cure her?

References

Jan 1, 1992·Journal of Inherited Metabolic Disease·G DarlingE Naughten
Mar 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J D McDonaldA Shedlovsky
Jul 29, 1993·The New England Journal of Medicine·P VajroO Bernard
Jul 1, 1996·European Journal of Pediatrics·W B HanleyV J Austin
May 15, 1998·The New England Journal of Medicine·I J FoxS C Strom
Nov 11, 1998·European Journal of Pediatrics·J PietzH J Bremer
Aug 13, 1999·Molecular Genetics and Metabolism·U Lichter-KoneckiD S Konecki
Feb 29, 2000·American Journal of Obstetrics and Gynecology·L D PlattE G Friedman
Nov 1, 2002·Journal of Inherited Metabolic Disease·R KochC Azen
Dec 7, 2002·Seminars in Cell & Developmental Biology·Ezio Laconi, Sergio Laconi
Oct 17, 1953·Lancet·H BICKELE M HICKMANS
Jan 8, 1955·British Medical Journal·L I WOOLFA MONCRIEFF
Aug 25, 1956·Journal of the American Medical Association·F A HORNER, C W STREAMER
Dec 1, 1956·Archives of Disease in Childhood·J D BLAINEY, R GULLIFORD
Feb 1, 1958·Archives of Disease in Childhood·L I WOOLFF DILLISTONE
Apr 1, 1955·The Journal of Clinical Investigation·M D ARMSTRONG, F H TYLER
Jan 20, 2004·Molecular Genetics and Metabolism·Nenad Blau, Charles R Scriver
May 20, 2004·International Journal of Adolescent Medicine and Health·John H Walter, Fiona J White
Jul 27, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kelly HammanCary O Harding
Feb 1, 1937·The Biochemical Journal·L Penrose, J H Quastel
Apr 23, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Sharon C CunninghamIan E Alexander
May 12, 2010·Journal of Inherited Metabolic Disease·Jean-Louis Dhondt
Aug 14, 2010·Journal of Bone and Mineral Metabolism·Piotr AdamczykWojciech Pluskiewicz
Nov 22, 2011·Human Gene Therapy·Lili WangJames M Wilson
Nov 10, 2012·Journal of Inherited Metabolic Disease·Julia B HennermannUwe Querfeld
Jan 5, 2013·Science·Le CongFeng Zhang
Jan 5, 2013·Science·Prashant MaliGeorge M Church
Apr 24, 2013·Molecular Genetics and Metabolism·Jo Ann V Antenor-DorseyDesirée A White
Jan 5, 2014·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Jerry VockleySusan A Berry
Jan 5, 2014·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Rani H SinghSandra C Van Calcar
Mar 4, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hiu Man ViecelliBeat Thöny

❮ Previous
Next ❯

Methods Mentioned

BETA
blood draw
targeted knockout

Software Mentioned

Molly

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Southwestern Medicine
L N NICKEY
The Southeast Asian Journal of Tropical Medicine and Public Health
J J McGill
Archives of Disease in Childhood
Elizabeth Hooley
© 2022 Meta ULC. All rights reserved